HCV is an enveloped positive-strand RNA virus in the Flaviviridae family. It contains a 9.6 kb genome starting at an untranslated region (5′-UTR), followed by sequences encoding structural proteins (core, E1, and E2) and non-structural (NS) proteins including p7, NS2, NS3, NS4 and NS5 (for review, see reference1,2). Unlike infection of hepatitis B virus (HBV), HCV infection is a multifaceted disease with both hepatic and extrahepatic manifestations3, and HCV can reside at non-hepatic cells4-6, which may play a role in viral persistence and reactivation. However, in vitro systems to investigate the extrahepatic replication of HCV have been severely limited. In terms of primary cells, direct infection of serum-borne HCV (HCVser) has been demonstrated only in human and chimpanzee hepatocytes, which are difficult to maintain in culture and also have significant donor-to-donor variations in cell properties. Furthermore, most in vitro cell culture methods employ molecular clones, not the natural virus (for review, see reference7). These models also grow viruses in non-primary cells, including the HLZ01 hepatoma cell line recently reported to support infection of clinical HCV isolates8. Therefore, how far the data can be extrapolated to the actual clinical virus-host interaction remains a concern.
Thus, there is still a need for alternative systems and methods of propagating serum-borne hepatitis C virus (HCV).